Immunology Graduate Group

David L. Gasser, Ph.D.
Professor, Genetics

Address: 575 CRB
Office Phone: 898-5175
Lab Phone: 898-5575
Fax: 573-5892
Email:  gasserd@mail.med.upenn.edu

Dr. Gasser's Cell & Molecular Biology page

Education:
Ph.D., University of Michigan
M.S., University of Michigan
B.S., University of Akron

Research Interest

Genetic basis of autoimmunity; interstitial nephritis in kdkd mice

Research Summary

We have cloned a mutant gene, kd , which was initially identified as a spontaneous mutation in a CBA colony. Mice that are homozygous for this allele begin life in an apparent state of health, but spontaneously develop a lethal kidney disease after the age of 3-6 months. This gene codes for an enzyme that is similar to trans-prenyltransferase, and is alternatively spliced as shown below. The gene product localizes to mitochondria, and the mitochondria of homozygous kdkd mice have defects that can be observed by electron microscopy.

Our research is directed toward the question of how this defect leads to an autoimmune reaction in the kidneys. We believe that the defect leads to apoptosis of renal tubular epithelial cells, and this in turn leads to an autoimmune response. The immune reaction involves multiple immune pathways, with effector T cells being involved, as well as NK cells. We have reason to believe that regulatory NKT cells also participate.

Recent Publications:

Dell KM, Li Y-X, Peng M, Neilson EG and Gasser DL. Localization of the mouse kidney disease ( kd ) gene to a YAC/BAC contig on Chromosome 10. Mammalian Genome 11: 967-971, 2000.

Hancock WW, Tsai T-L, Madaio MP and Gasser DL. Cutting edge: Multiple autoimmune pathways in kd/kd mice. J. Immunol . 171: 2778-2781, 2003.

Peng M, Jarett L, Meade R, Madaio MP, Hancock WW, George AL , Neilson EG and Gasser DL. Mutant prenyltransferase-like mitochondrial protein (PLMP) and mitochondrial abnormalities in kd/kd mice. Kidney International 66: 20-28, 2004.

Madaio, M. P., Ahima, R.S., Meade, R., Rader D.J., Mendoza, A., Peng, M., Tomaszewski, J. E., Hancock, W. W. and Gasser, D. L.: Glomerular and tubular epithelial defects in kd/kd mice lead to progressive renal failure. Am. J. Nephrol. 25: 604-610, 2005.

Hallman, T.M., Peng, M., Meade, R., Hancock, W.W., Madaio, M.P. and Gasser, D.L.: The mitochondrial and kidney disease phenotypes of kd/kd mice under germfree conditions. Journal of Autoimmunity 26: 1-6, 2006.

 

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